Resveratrol / BioAv Cancer Research Results

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


BioAv, bioavailability: Click to Expand ⟱
Source:
Type: measurement
Bioavailability (usually in %) absorbed by the body.


Scientific Papers found: Click to Expand⟱
3076- RES,    Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells
- Review, Var, NA
IL6↓, MMPs↓, MMP2↓, MMP9↓, BioAv↓, Half-Life↑, BioAv↑, Dose↝, angioG↓, IL10↓, VEGF↓, NF-kB↓, COX2↓, SIRT1↑, Wnt↓, cMyc↓, STAT3↓, PTEN↑, ROS↑, RadioS↑, Hif1a↓, E-cadherin↓, Vim↓, angioG↓,
3100- RES,    Neuroprotective effects of resveratrol in Alzheimer disease pathology
- Review, AD, NA
*neuroP↑, *BioAv↓, *Half-Life↓, *BioAv↑, *BBB↑, *NRF2↑, *BioAv↓, *BioAv↑, *SIRT1↑, *cognitive↑, *lipid-P↓, *HO-1↑, *SOD↑, *GSH↑, *GPx↑, *G6PD↑, *PPARγ↑, *AMPK↑, *Aβ↓,
3099- RES,    Resveratrol and cognitive decline: a clinician perspective
- Review, Nor, NA - NA, AD, NA
*antiOx↑, *ROS↓, *cognitive↑, *neuroP↑, *SIRT1↑, *AMPK↑, *GPx↑, *HO-1↑, *GSK‐3β↑, *COX2↓, *PGE2↓, *NF-kB↓, *NO↓, *Casp3↓, *MMP3↓, *MMP9↓, *MMP↑, *GSH↑, *other↑, *BioAv↑, *memory↑, *GlutMet↑, *BioAv↓, *Half-Life↓, *toxicity∅,
1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑, ChemoSen↑, *BioAv↓, *BioAv↑, Ferroptosis↑, lipid-P↑, xCT↓, GPx4↓, *BioAv↑, COX2↓, cycD1/CCND1↓, FasL↓, FOXP3↓, HLA↑, p‑NF-kB↓, BAX↑, Bcl-2↓, MALAT1↓,
1490- RES,    Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues
- Review, Var, NA
TumCCA↑, ROS↑, Ca+2↑, MMP↓, ATP↓, TOP1?, P53↑, p53 Wildtype∅, Akt↓, mTOR↓, EMT↓, *BioAv↓,
3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, BioAv↓, Dose↑, eff↑, eff↑, Dose↑, BioAv↑, ROS↑, MMP↓, P21↑, p27↑, TumCCA↑, ChemoSen↑, COX2↓, 5LO↓, VEGF↓, IL1↓, IL6↓, IL8↓, AR↓, PSA↓, MAPK↓, Hif1a↓, Glycolysis↓, miR-21↓, PTEN↑, Half-Life↝, *IGF-1↓, *IGFBP3↑, Half-Life↓,
2442- RES,    High absorption but very low bioavailability of oral resveratrol in humans
- in-vitro, Nor, NA
BioAv↝, Half-Life↝, BioAv↓, eff↝,
2687- RES,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, NA, NA - Review, AD, NA
NF-kB↓, P450↓, COX2↓, Hif1a↓, VEGF↓, *SIRT1↑, SIRT1↓, SIRT2↓, ChemoSen⇅, cardioP↑, *memory↑, *angioG↑, *neuroP↑, STAT3↓, CSCs↓, RadioS↑, Nestin↓, Nanog↓, TP53↑, P21↑, CXCR4↓, *BioAv↓, EMT↓, Vim↓, Slug↓, E-cadherin↑, AMPK↑, MDR1↓, DNAdam↑, TOP2↓, PTEN↑, Akt↓, Wnt↓, β-catenin/ZEB1↓, cMyc↓, MMP7↓, MALAT1↓, TCF↓, ALDH↓, CD44↓, Shh↓, IL6↓, VEGF↓, eff↑, HK2↓, ROS↑, MMP↓,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,
2650- RES,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, Dose↝, NRF2↑, NAF1↓, ChemoSen↑, BioAv↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

Ferroptosis↑, 1,   GPx4↓, 1,   lipid-P↑, 1,   NAF1↓, 1,   NRF2↑, 1,   ROS↑, 5,   xCT↓, 1,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis

AMPK↑, 1,   cMyc↓, 2,   Glycolysis↓, 1,   HK2↓, 1,   SIRT1↓, 1,   SIRT1↑, 1,   SIRT2↓, 1,  

Cell Death

Akt↓, 2,   BAX↑, 1,   Bcl-2↓, 1,   FasL↓, 1,   Ferroptosis↑, 1,   MAPK↓, 1,   p27↑, 1,  

Transcription & Epigenetics

miR-21↓, 1,  

DNA Damage & Repair

DNAdam↑, 1,   P53↑, 1,   p53 Wildtype∅, 1,   TP53↑, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

ALDH↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 2,   mTOR↓, 1,   Nanog↓, 1,   Nestin↓, 1,   PTEN↑, 3,   Shh↓, 1,   STAT3↓, 2,   TCF↓, 1,   TOP1?, 1,   TOP2↓, 1,   Wnt↓, 2,  

Migration

5LO↓, 1,   Ca+2↑, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   HLA↑, 1,   MALAT1↓, 2,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Slug↓, 1,   Vim↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

angioG↓, 2,   Hif1a↓, 3,   VEGF↓, 4,  

Immune & Inflammatory Signaling

COX2↓, 4,   CXCR4↓, 1,   FOXP3↓, 1,   IL1↓, 1,   IL10↓, 1,   IL6↓, 3,   IL8↓, 1,   NF-kB↓, 2,   p‑NF-kB↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 5,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 3,   ChemoSen⇅, 1,   Dose↑, 2,   Dose↝, 2,   eff↑, 5,   eff↝, 1,   Half-Life↓, 1,   Half-Life↑, 1,   Half-Life↝, 2,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 3,  

Clinical Biomarkers

AR↓, 1,   IL6↓, 3,   PSA↓, 1,   TP53↑, 1,  

Functional Outcomes

cardioP↑, 1,  
Total Targets: 92

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   GPx↑, 2,   GSH↑, 2,   H2O2↓, 1,   HO-1↑, 3,   lipid-P↓, 1,   mt-lipid-P↓, 1,   MDA↓, 1,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics

ATP↑, 1,   MMP↑, 2,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 3,   G6PD↑, 1,   GlutMet↑, 1,   NADH:NAD↑, 1,   PPARγ↑, 2,   SIRT1↑, 4,  

Cell Death

Casp3↓, 1,   Cyt‑c∅, 1,  

Transcription & Epigenetics

other↑, 1,  

Protein Folding & ER Stress

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State

FOXO↑, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   IGF-1↓, 1,   IGFBP3↑, 1,  

Migration

AntiAg↑, 1,   MMP3↓, 1,   MMP9↓, 2,  

Angiogenesis & Vasculature

angioG↑, 1,   NO↓, 1,  

Barriers & Transport

BBB↓, 1,   BBB↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   IL1β↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 7,   BioAv↑, 5,   eff↑, 3,   Half-Life↓, 2,   Half-Life↝, 1,  

Clinical Biomarkers

BP↓, 1,  

Functional Outcomes

cognitive↑, 2,   memory↑, 2,   motorD↑, 1,   neuroP↑, 4,   toxicity∅, 1,  
Total Targets: 59

Scientific Paper Hit Count for: BioAv, bioavailability
10 Resveratrol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:792  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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